Malignant Hyperthermia

1. MALIGNANT MALIGNANT
HYPERTHERMIAHYPERTHERMIA
Dr. Shailendra.V.L.Dr. Shailendra.V.L.
Specialist in Anesthesia,Specialist in Anesthesia,
Al Bukariya general hospitalAl Bukariya general hospital

2. CASE HISTORYCASE HISTORY
A 5 year old boy for tonsillectomy & A 5 year old boy for tonsillectomy &
adenoidectomy adenoidectomy was induced with was induced with
halothane halothane by by mask. mask. Three minutes Three minutes
later, succinylcholine is given. Mild later, succinylcholine is given. Mild
muscle rigidity of the jaw is noted, but muscle rigidity of the jaw is noted, but
intubation is accomplished. The childintubation is accomplished. The child
is noted to develop a is noted to develop a bradycardiac bradycardiac
cardiac cardiac arrest. arrest. ( asystole )( asystole )

3. CASE HISTORYCASE HISTORY
A 9 year old girl develops masseter A 9 year old girl develops masseter
muscle rigidity after propofol muscle rigidity after propofol
induction and succinylcholine induction and succinylcholine
administration. Rigidity of the administration. Rigidity of the
arms is also noted. But end - tidalarms is also noted. But end - tidal
CO2 is normalCO2 is normal

4. CASE HISTORYCASE HISTORY
A 16 year old patient was maintained on A 16 year old patient was maintained on
isoflurane and vecuronium. At the end of isoflurane and vecuronium. At the end of
the surgery, she is breathing 20 times per the surgery, she is breathing 20 times per
minute and her end-tidal CO2 is 65mm minute and her end-tidal CO2 is 65mm
Hg. She suddenly develops ventricular Hg. She suddenly develops ventricular
premature contractions. Her forehead premature contractions. Her forehead
skin temperature is 99 F. skin temperature is 99 F.

5. DEFINITION OF M HDEFINITION OF M H
It is charecterised by hyper It is charecterised by hyper
metabolic response to potent inhalation metabolic response to potent inhalation
agents and succinylcholine resulting in agents and succinylcholine resulting in
increased CO2 production, oxygen increased CO2 production, oxygen
consumption, fever, tachycardia, consumption, fever, tachycardia,
tachypnoea, acidosis, hyperkalemia, tachypnoea, acidosis, hyperkalemia,
myoglobinuria, increased CPK, myoglobinuria, increased CPK,
cyanosis & death cyanosis & death

6. HISTORY OF M HHISTORY OF M H
1960: 1960: Critical worldwide insight into MH Critical worldwide insight into MH
began when Denborough & Lovell described began when Denborough & Lovell described
a 21 year Australian, with an open leg # who a 21 year Australian, with an open leg # who
was more anxious about anaesthesia, because was more anxious about anaesthesia, because
10 of his relatives had died during anaesthesia10 of his relatives had died during anaesthesia..
1966:1966: Hall reported on MH induced by Hall reported on MH induced by
halothane & succinylcholine in swines. The halothane & succinylcholine in swines. The
human & porcine forms are virtually identical.human & porcine forms are virtually identical.
1975:1975: Harrison described efficacy of Harrison described efficacy of
Dantrolene in preventing & treating porcine Dantrolene in preventing & treating porcine
MH, which was confirmed in humans.MH, which was confirmed in humans.

7. INCIDENCE OF M HINCIDENCE OF M H
1 in 12,000 pediatric anesthetics1 in 12,000 pediatric anesthetics
1 in 40,000 adult anesthetics1 in 40,000 adult anesthetics
Incidence has an apparent geographic Incidence has an apparent geographic
variation – more prevalent in USvariation – more prevalent in US
2/3 of susceptible patients manifest 2/3 of susceptible patients manifest
this syndrome during their first this syndrome during their first
anestheticanesthetic

8. GENETICS OF M HGENETICS OF M H
Three modes of inheritanceThree modes of inheritance::
•Autosomal dominantAutosomal dominant
•Autosomal recessiveAutosomal recessive
•UnclassifiedUnclassified
 The Gene for MH is located The Gene for MH is located
on Chromosome 19, which is also on Chromosome 19, which is also
the genetic coding site for the genetic coding site for RyanodineRyanodine
receptors receptors ( Calcium release channel)( Calcium release channel)
of skeletal muscle sarcoplasmic reticulumof skeletal muscle sarcoplasmic reticulum

9. PATHOPHYSIOLOGY OF MHPATHOPHYSIOLOGY OF MH
Defect in excitation—contraction coupling of Defect in excitation—contraction coupling of
calcium in the sarcolemma in the musclecalcium in the sarcolemma in the muscle
The basic defect lies in the muscle fiber The basic defect lies in the muscle fiber
involving cellular membrane permeability of involving cellular membrane permeability of
the sarcoplasmic reticulum, which results in an the sarcoplasmic reticulum, which results in an
inability to control calcium concentrations inability to control calcium concentrations
within the fiber. within the fiber.
The resultant events are heat production & The resultant events are heat production &
muscle contracture secondary to enhanced muscle contracture secondary to enhanced
glycolysis, uncoupling of oxidative glycolysis, uncoupling of oxidative
phosphorylation, & activation of actin-myosin phosphorylation, & activation of actin-myosin
filaments.filaments.

10. TRIGERING AGENTS FOR MHTRIGERING AGENTS FOR MH
IN ORDER OR THEIR TRIGERRING POTENTIAL:IN ORDER OR THEIR TRIGERRING POTENTIAL:
HalothaneHalothane
EnfluraneEnflurane
IsofluraneIsoflurane
DesfluraneDesflurane
SevofloraneSevoflorane
EtherEther
ChloroformChloroform
SuxamethoniumSuxamethonium

11. SIGNS OF M HSIGNS OF M H
TachycardiaTachycardia
TachypnoeaTachypnoea
Arterial hypoxemiaArterial hypoxemia
HypercarbiaHypercarbia
Metabolic & Respiratory acidosisMetabolic & Respiratory acidosis
HyperkalemiaHyperkalemia
Cardiac arrhythmias Cardiac arrhythmias
HypotensionHypotension
Skeletal muscle rigidity ( masseter spasm ) Skeletal muscle rigidity ( masseter spasm )
Increased body temperatureIncreased body temperature
Increased CPK levels – 20,000 I.U.Increased CPK levels – 20,000 I.U.

12. EARLY DIAGNOSTIC EARLY DIAGNOSTIC
SIGNS OF MHSIGNS OF MH
Rising end-tidal CO2 concentration Rising end-tidal CO2 concentration
Inappropriate tachycardiaInappropriate tachycardia
Hypertension, hypoxemia & acidosisHypertension, hypoxemia & acidosis

13. INVESTIGATIONSINVESTIGATIONS
Capnograph:Capnograph:
•Rising EtCO2Rising EtCO2
Pulse oximeter:Pulse oximeter:
•Falling saturationFalling saturation
ECG monitor: ECG monitor:
•Tachycardia Tachycardia
•ArrythmiasArrythmias
- Ventricular bigemeny- Ventricular bigemeny
-Multifocal premature beatsMultifocal premature beats
-Ventricular fibrillationVentricular fibrillation
-Ventricular tachycardiaVentricular tachycardia

14. INVESTIGATIONSINVESTIGATIONS
ABG:ABG:
•Arterial hypoxemiaArterial hypoxemia
•Hypercarbia ( 100 to 200 mm of Hg ) Hypercarbia ( 100 to 200 mm of Hg )
•Respiratory & metabolic acidosis( Ph 7.15 to 6.8)Respiratory & metabolic acidosis( Ph 7.15 to 6.8)
Electrolytes:Electrolytes:
•Hyperkalemia ( > than 6 mEq )Hyperkalemia ( > than 6 mEq )
•Raised transaminase enzymes Raised transaminase enzymes
•Markedly elevated CPK ( > 20,000 IU ) Markedly elevated CPK ( > 20,000 IU )
( peak levels after 12 to 24 hours of the episode )( peak levels after 12 to 24 hours of the episode )
 Plasma & urine myoglobin elevatedPlasma & urine myoglobin elevated

15. COMPLICATIONS OF M HCOMPLICATIONS OF M H
DICDIC
Pulmonary edemaPulmonary edema
Acute renal failureAcute renal failure
CNS damageCNS damage
•blindness, seizures, coma, paralysisblindness, seizures, coma, paralysis
CVS manifestationsCVS manifestations
•arrythmiasarrythmias

16. Differential diagnosis for MHDifferential diagnosis for MH
Neuroleptic malignant syndromeNeuroleptic malignant syndrome
Thyrotoxic crisisThyrotoxic crisis
Cocaine toxicityCocaine toxicity
Heat strokeHeat stroke
Serotonin syndromeSerotonin syndrome
Status epilepticusStatus epilepticus
PheochromocytomaPheochromocytoma

17. TREATMENT OF M HTREATMENT OF M H
Etiologic treatment:Etiologic treatment:
•DantroleneDantrolene ( 2 – 3 mg/kg IV) as an ( 2 – 3 mg/kg IV) as an
initialinitial bolus, bolus, followed with repeat followed with repeat
doses doses every every 5 – 105 – 10 minutes minutes until until
symptoms symptoms areare controlled. controlled.
•Prevent recurrence (dantrolene 1 mg / Prevent recurrence (dantrolene 1 mg /
kg kg IV IV every every 6 6 hours for 72 hours )hours for 72 hours )

18. TREATMENT OF M HTREATMENT OF M H
Symptomatic Treatment:Symptomatic Treatment:
Immediately terminate trigger drugs Immediately terminate trigger drugs
& & concludeconclude surgery surgery as as soonsoon
as possibleas possible
HyperventilateHyperventilate with with 100 %100 % oxygen oxygen
Initiate active cooling Initiate active cooling
•Iced saline 15 ml / kg every 10 minutesIced saline 15 ml / kg every 10 minutes
•Gatric Gatric lavagelavage with with iced iced saline saline
•Surface Surface cooling cooling

19. TREATMENT OF M HTREATMENT OF M H
Symptomatic treatment:Symptomatic treatment:
Correct metabolic acidosis ( NaHCO3 1 Correct metabolic acidosis ( NaHCO3 1
– 2 m Eq/kg IV based on arterial ph– 2 m Eq/kg IV based on arterial ph
Maintain urine outputMaintain urine output
HydrationHydration
Mannitol ( 0.25 g/kg IV )Mannitol ( 0.25 g/kg IV )
Furosemide ( 1mg/ kg )Furosemide ( 1mg/ kg )
Treatment of arrythmiasTreatment of arrythmias
Xylocaine infusionXylocaine infusion
Monitor in ICUMonitor in ICU

20. IDENTIFICATION OF IDENTIFICATION OF
SUSECPTIBLE PATIENTSSUSECPTIBLE PATIENTS
A detailed medical & family historyA detailed medical & family history
Myopathic syndromesMyopathic syndromes
•Duchenne muscular dystrophyDuchenne muscular dystrophy
•Myotonia congenitaMyotonia congenita
•Pectus carinatumPectus carinatum
•KyphoscoliosisKyphoscoliosis
•Ostoegenis imperfectaOstoegenis imperfecta

21. IDENTIFICATION OF IDENTIFICATION OF
SUSEPTIBLE PATIENTSSUSEPTIBLE PATIENTS
Laboratory investigations:Laboratory investigations:
•CPK levels ( 70% suseptibles have CPK levels ( 70% suseptibles have
elevated resting CPK levels )elevated resting CPK levels )
•Electromyographic studies ( 50% Electromyographic studies ( 50%
suseptibles show changes )suseptibles show changes )

22. IDENTIFICATION OF IDENTIFICATION OF
SUSEPTIBLE PATIENTSSUSEPTIBLE PATIENTS
Skeletal muscle biopsy:Skeletal muscle biopsy:
•TakenTaken from from vastusvastus muscle muscle of thigh of thigh
under under local local anaesthesia.anaesthesia.
•MuscleMuscle is is subjectedsubjected to to isometric isometric
contracture testing under influence of contracture testing under influence of
caffeinecaffeine or or halothane halothane or or both. both. It It
producesproduces exaggerated exaggerated contracture in contracture in
susceptible patients.susceptible patients.

23. MANAGEMENT MANAGEMENT
OFANAESTHESIAOFANAESTHESIA
“ “AVOID ALL TRIGGERING DRUGS ”AVOID ALL TRIGGERING DRUGS ”
“ “ Regional blocks are preferred ”Regional blocks are preferred ”
 Premedication: Premedication: barbiturates barbiturates or or
benzodiazepines can safely be usedbenzodiazepines can safely be used
 Dantrolene prophylaxis adminstration Dantrolene prophylaxis adminstration
is controversialis controversial

24. MANAGEMENT OF ANAESTHESIAMANAGEMENT OF ANAESTHESIA
Pre-oxygenation for three minutesPre-oxygenation for three minutes
Induction: thiopentone / propofolInduction: thiopentone / propofol
Intubation : non depolarizing relaxantsIntubation : non depolarizing relaxants
Maintainance: oxygen + nitrous oxideMaintainance: oxygen + nitrous oxide
Reversal: neosigmine + atropineReversal: neosigmine + atropine

25. MANAGEMENT OF MANAGEMENT OF
ANAESTHESIAANAESTHESIA
 Anaesthesia machine without vaporisers Anaesthesia machine without vaporisers
 New face mask and circle absorberNew face mask and circle absorber
 New breathing circuit & reservoir bagNew breathing circuit & reservoir bag
Monitors:Monitors:
• ECG monitorECG monitor
• NIBP monitorNIBP monitor
• Pulse oximeterPulse oximeter
• End-tidal CO2 monitorEnd-tidal CO2 monitor
• TemperatureTemperature

26. NON-TRIGGERING AGENTS NON-TRIGGERING AGENTS
FOR MHFOR MH
BarbituratesBarbiturates
OpioidsOpioids
PropofolPropofol
BenzodiazepinesBenzodiazepines
Nitrous oxideNitrous oxide
Anti-cholinergicsAnti-cholinergics
Anti-cholinesterasesAnti-cholinesterases
Local anaestheticsLocal anaesthetics
SympathomineticsSympathominetics

27. REFERENCESREFERENCES
 Anaesthesia & co-existing diseases – Anaesthesia & co-existing diseases –
Stoelting.Stoelting.
 Short practice of Anaesthesia – Churchill Short practice of Anaesthesia – Churchill
DavidsonDavidson
 Problem oriented Anaesthesia – Stoelting.Problem oriented Anaesthesia – Stoelting.
 American Society of Anaesthesia ( ASA )American Society of Anaesthesia ( ASA )
Annual refresher lecture notes – 1998.Annual refresher lecture notes – 1998.
 Textbook of Anaesthesia – Ronald Miller.Textbook of Anaesthesia – Ronald Miller.